Antisense-mediated inhibition of the bcl-2 gene induces apoptosis in human malignant glioma

Julien, Terrence; Frankel, Bruce; Longo, Sharon L.; Kyle, Michele; Gibson, Sandra; Shillitoe, Edward J.; Ryken, Timothy C.

doi:10.1016/s0090-3019(00)00178-6

Cited by 37 publications

(22 citation statements)

References 26 publications

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“…These findings are consistent with previous reports that demonstrate PAX expression enhances cell growth and survival [15,42], and upregulated BCL2 is found in gliomagenesis [21,31]. In other studies BCL2 silencing induced cell death in vitro [43,44], led to an arrest of cell cycle progression [19], and was associated with the downregulation of multiple developmental genes [45]. …”

Section: Discussionsupporting

confidence: 92%

Increased paired box transcription factor 8 has a survival function in Glioma

et al. 2014

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BackgroundThe molecular basis to overcome therapeutic resistance to treat glioblastoma remains unclear. The anti-apoptotic b cell lymphoma 2 (BCL2) gene is associated with treatment resistance, and is transactivated by the paired box transcription factor 8 (PAX8). In earlier studies, we demonstrated that increased PAX8 expression in glioma cell lines was associated with the expression of telomerase. In this current study, we more extensively explored a role for PAX8 in gliomagenesis.MethodsPAX8 expression was measured in 156 gliomas including telomerase-negative tumours, those with the alternative lengthening of telomeres (ALT) mechanism or with a non-defined telomere maintenance mechanism (NDTMM), using immunohistochemistry and quantitative PCR. We also tested the affect of PAX8 knockdown using siRNA in cell lines on cell survival and BCL2 expression.ResultsSeventy-two percent of glioblastomas were PAX8-positive (80% telomerase, 73% NDTMM, and 44% ALT). The majority of the low-grade gliomas and normal brain cells were PAX8-negative. The suppression of PAX8 was associated with a reduction in both cell growth and BCL2, suggesting that a reduction in PAX8 expression would sensitise tumours to cell death.ConclusionsPAX8 is increased in the majority of glioblastomas and promoted cell survival. Because PAX8 is absent in normal brain tissue, it may be a promising therapeutic target pathway for treating aggressive gliomas.

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Section: Discussionsupporting

confidence: 92%

Increased paired box transcription factor 8 has a survival function in Glioma

et al. 2014

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“…Moreover, up-regulation of antiapoptotic Bcl - xl gene with concurrent overexpression of EGFRvIII can be a cause of resistance to cisplatin agent [30]. Usage of Bcl2 specific antisense oligonucleotides activates apoptosis and may be helpful in treatment [31]. In our study, we found a positive correlation between expression of WWOX and the antiapoptotic gene Bcl2 .…”

Section: Discussionsupporting

confidence: 54%

Molecular analysis of WWOX expression correlation with proliferation and apoptosis in glioblastoma multiforme

et al. 2010

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Glioblastoma multiforme is the most common type of primary brain tumor in adults. WWOX is a tumor suppressor gene involved in carcinogenesis and cancer progression in many different neoplasms. Reduced WWOX expression is associated with more aggressive phenotype and poor patient outcome in several cancers. We investigated alternations of WWOX expression and its correlation with proliferation, apoptosis and signal trafficking in 67 glioblastoma multiforme specimens. Moreover, we examined the level of WWOX LOH and methylation status in WWOX promoter region. Our results suggest that loss of heterozygosity (relatively frequent in glioblastoma multiforme) along with promoter methylation may decrease the expression of this tumor suppressor gene. Our experiment revealed positive correlations between WWOX and Bcl2 and between WWOX and Ki67. We also confirmed that WWOX is positively correlated with ErbB4 signaling pathway in glioblastoma multiforme.

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“…The inhibition of Bcl-2 using antisense constructs results in tumor cell death in vitro (Jiang et al 2003;Julien et al 2000). Therefore, targeting Bcl-2 may provide a therapeutic benefit by countering its antiapoptotic effects.…”

Section: Discussionmentioning

confidence: 99%